Human Papillomavirus-16 E7 Interacts with Glutathione S-Transferase P1 and Enhances Its Role in Cell Survival

Background:Human Papillomavirus (HPV)-16 is a paradigm for "high-risk" HPVs, the causative agents of virtually all cervical carcinomas. HPV E6 and E7 viral genes are usually expressed in these tumors, suggesting key roles for their gene products, the E6 and E7 oncoproteins, in inducing malignant transformation.Methodology/Principal Findings:By protein-protein interaction analysis, using mass spectrometry, we identified glutathione S-transferase P1-1 (GSTP1) as a novel cellular partner of the HPV-16 E7 oncoprotein. Following mapping of the region in the HPV-16 E7 sequence that is involved in the interaction, we generated a three-dimensional molecular model of the complex between HPV-16 E7 and GSTP1, and used this to engineer a mutant molecule of HPV-16 E7 with strongly reduced affinity for GSTP1.When expressed in HaCaT human keratinocytes, HPV-16 E7 modified the equilibrium between the oxidized and reduced forms of GSTP1, thereby inhibiting JNK phosphorylation and its ability to induce apoptosis. Using GSTP1-deficient MCF-7 cancer cells and siRNA interference targeting GSTP1 in HaCaT keratinocytes expressing either wild-type or mutant HPV-16 E7, we uncovered a pivotal role for GSTP1 in the pro-survival program elicited by its binding with HPV-16 E7.Conclusions/Significance:This study provides further evidence of the transforming abilities of this oncoprotein, setting the groundwork for devising unique molecular tools that can both interfere with the interaction between HPV-16 E7 and GSTP1 and minimize the survival of HPV-16 E7-expressing cancer cells. © 2009 Mileo et al

Neglected diseases of neglected populations: Thinking to reshape the determinants of health in Latin America and the Caribbean

BACKGROUND: People living in poverty throughout the developing world are heavily burdened with neglected communicable diseases and often marginalized by the health sector. These diseases are currently referred to as Neglected Diseases of Neglected Populations. The neglected diseases create social and financial burdens to the individual, the family, the community, and the nation. DISCUSSION: Numerous studies of successful individual interventions to manage communicable disease determinants in various types of communities have been published, but few have applied multiple interventions in an integrated, coordinated manner. We have identified a series of successful interventions and developed three hypothetical scenarios where such interventions could be applied in an integrated, multi-disease, inter-programmatic, and/or inter-sectoral approach for prevention and control of neglected diseases in three different populations: a slum, an indigenous community, and a city with a mix of populations. SUMMARY: The objective of this paper is to identify new opportunities to address neglected diseases, improve community health and promote sustainable development in neglected populations by highlighting examples of key risk and protective factors for neglected diseases which can be managed and implemented through multi-disease-based, integrated, inter-programmatic, and/or inter-sectoral approaches. Based on a literature review, analysis and development of scenarios we visualize how multiple interventions could manage multiple disease problems and propose these as possible strategies to be tested. We seek to stimulate intra- and inter-sectoral dialogue which will help in the construction of new strategies for neglected diseases (particularly for the parasitic diseases) which could benefit the poor and marginalized based on the principle of sustainability and understanding of key determinants of health, and lead to the establishment of pilot projects and activities which can contribute to the achievement of the Millennium Development Goals

Selection of non-timber forest species for community and private plantations in the high and low altitude areas of Makawanpur District, Nepal

The domestication of non-timber forest species (NTFS) is receiving increasing attention from developing economies. However, little is known about the selection of NTFS in Nepal for commercial uses. Sixteen selection criteria were developed and NTFS were ranked for community and private plantations in both low altitude and high altitude areas of Makawanpur district, Nepal, by workshops of multiple NTFS stakeholders. The rigorous scoring of 12 ecologically screened NTFS against the 16 selection criteria revealed that kurilo and sarpagandh are highly preferred NTFS for low altitude areas whereas chiraito and jatamanshi are highly preferred for high altitude. This finding coincides with the general perception of participants and contemporary literature. These are the species being rapidly depleted from the natural forests. Rapid decline of valuable species creates strong motivation from stakeholders for planting them on community and private lan

Carbon sequestration potential of <i>Alnus nepalensis</i> in the mid hill of Nepal: A case study from Kaski district

This study was carried out to analyze the carbon content in different parts of Alnus nepalensis, and to assess the effect of aspect and altitude in the carbon storage in Alnus nepalensis as well as to quantify the total carbon sequestration (stock) in Alnus nepalensis forest in the mid-hills of Kaski District. The inventory for estimating above and below ground biomass of forest was carried out using stratified random sampling technique. The carbon content in different parts of Alnus nepalensis was quantified using combustion method in the laboratory. For determining the soil carbon content, six soil profiles from each aspect were excavated and soil samples were taken from soil profile up to 1 m depth for deep soil and up to bedrock for shallow soils at the interval of 20 cm. Mean carbon content in stem, branches, leaves and bark of Alnus nepalensis were found to be 40.52%, 33%, 9.56% and 16.4%, respectively. Total biomass carbon sequestered in northern aspect was 30.20 t/ha while for southern aspect it was 39.00 t/ha. In both the aspects higher carbon sequestration was observed at an elevation range of 1200-1300m i.e. 34.8 t/ha and 45.6 t/ha in northern and southern aspects, respectively. Soil carbon sequestration in northern and southern aspects was found to be 113.4 t/ha and 169.30 t/ ha, respectively. The total carbon sequestration potential of Alnus nepalensis forest was estimated to be 186.05 t/ha. Key words: Alnus nepalensis, altitude, aspect, carbon sequestration, mid hills   doi: 10.3126/banko.v18i2.2167 Banko Janakari, Vol. 18, No. 2, 3-9</jats:p

Cervical Sympathetic Chain Schwannoma: A Case Report

Tumors originating in the parapharyngeal space are rare and are fascinating to the surgeon in view of the anatomical complexity of the area, varied histological type of tumors encountered and the impressive size which some of these tumors attain before becoming clinically evident. We report a rare case of schwannoma arising from the cervical sympathetic chain presenting as a mass in the parapharyngeal space